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Elisabet Alzueta,1 Massimiliano de Zambotti,1 Harold Javitz,2 Teji Dulai,1 Benedetta Albinni,1,3 Katharine C Simon,4 Negin Sattari,4 Jing Zhang,4 Alessandra Shuster,4 Sara C Mednick,4 Fiona C Baker1,5 1Center for Health Sciences, SRI International, Menlo Park, CA, USA; 2Division of Education, SRI International, Menlo Park, CA, USA; 3Department of Psychology, University of Campania L. Vanvitelli, Italy; 4Department of Cognitive Science, University of California, Irvine, CA, USA; 5School of Physiology, University of the Witwatersrand, Johannesburg, South AfricaCorrespondence: Fiona C Baker, SRI International, 333 Ravenswood Avenue, Menlo Park, CA, 94025, USA, Email Fiona.baker@sri.comBackground and Objective: The ovulatory menstrual cycle is characterized by hormonal fluctuations that influence physiological systems and functioning. Multi-sensor wearable devices can be sensitive tools capturing cycle-related physiological features pertinent to women’s health research. This study used the Oura ring to track changes in sleep and related physiological features, and also tracked self-reported daily functioning and symptoms across the regular, healthy menstrual cycle.Methods: Twenty-six healthy women (age, mean (SD): 24.4 (1.1 years)) with regular, ovulatory cycles (length, mean (SD): 28.57 (3.8 days)) were monitored across a complete menstrual cycle. Four menstrual cycle phases, reflecting different hormone milieus, were selected for analysis: menses, ovulation, mid-luteal, and late-luteal. Objective measures of sleep, sleep distal skin temperature, heart rate (HR) and vagal-mediated heart rate variability (HRV, rMSSD), derived from the Oura ring, and subjective daily diary measures (eg sleep quality, readiness) were compared across phases.Results: Wearable-based measures of sleep continuity and sleep stages did not vary across the menstrual cycle. Women reported no menstrual cycle-related changes in perceived sleep quality or readiness and only marginally poorer mood in the midluteal phase. However, they reported moderately more physical symptoms during menses (p < 0.001). Distal skin temperature and HR, measured during sleep, showed a biphasic pattern across the menstrual cycle, with increased HR (p < 0.03) and body temperature (p < 0.001) in the mid- and late-luteal phases relative to menses and ovulation. Correspondingly, rMSSD HRV tended to be lower in the luteal phase. Further, distal skin temperature was lower during ovulation relative to menses (p = 0.05).Conclusion: The menstrual cycle was not accompanied by significant fluctuations in objective and perceived measures of sleep or in mood, in healthy women with regular, ovulatory menstrual cycles. However, other physiological changes in skin temperature and HR were evident and may be longitudinally tracked with the Oura ring in women over multiple cycles in a natural setting.Keywords: sleep, wearables, menstrual cycle, ovulation, body temperature, women’s health

The article presents a study which examines the risk factors for neuromyelitis optica (NMO) or transverse myelitis (TM) and their association with multiple sclerosis (MS) risk factors. The study is investigated by case-control method, enzyme-linked immunosorbent assay ( ELISA), and serum sampling. Results show that MS risk factors are not correlated with susceptibility to TM or NMO.

Purpose: The association between infectious mononucleosis (IM) and risk of breast cancer is unclear; no prospective studies have examined this relationship. We examined self-reported history and age at IM in relation to risk of invasive breast cancer.Methods: Self-reported history and age at IM were examined in relation to risk of invasive breast cancer in a large cohort of women, the Nurses' Health Study II (81,807 women followed from 1989 to 2007). Through questionnaires, women were asked whether they ever had IM and if so, at what age. During follow-up, 2,349 cases of invasive breast cancer were documented. Cox proportional hazards regression was used to estimate relative risks (RR) and 95 % confidence intervals (CI) for the association of IM with breast cancer.Results: The multivariable-adjusted RR for history of IM and risk of invasive breast cancer was 1.00 (95 % CI: 0.90-1.11). Similar null results were obtained when estrogen receptor/progesterone receptor positive and negative tumors were considered separately. There were no clear patterns of association between age at IM and risk of breast cancer: compared to women with no history of IM, those who were ≤15 years old when they had IM were at lower risk (RR: 0.77; 95 % CI: 0.60, 0.97), but there was no association for women who had IM at ages 16-19, 20-24, or 30+. However, an increased RR (1.45; 95 % CI: 1.02-2.04) was observed for women who had IM at ages 25-29.Conclusion: Results of this large prospective study do not support a clear association between history of clinical IM and risk of invasive breast cancer. [ABSTRACT FROM AUTHOR]

The sharing of personal memories is a unique aspect of the human experience. Humans communicate to provide information, to influence, or even to amuse. How do we distinguish between credible and noncredible narratives? Forensic science has identified race, age, and detail quantity as influential. We do not know how the nature of narrated details impacts believability. We report two studies investigating how detail composition influences credibility ratings using definitions of details suggested by Levine et al. (2002). Internal details are directly connected to the episodic aspects of the memory, while external details refer to semantic facts or depictions not directly related to the main event. A total of 825 participants rated narratives that varied detail number and type for perceived credibility or saliency. Episodic memory details enhanced credibility more than semantic memory details. In addition, within episodic memories, person-related details enhanced credibility more than non-person-related details. Our results suggest a lens through which to view the credibility of what we hear and read., Competing Interests: Competing interests statement:The authors declare no competing interest.

Emotional memories change over time, but the mechanisms supporting this change are not well understood. Sleep has been identified as one mechanism that supports memory consolidation, with sleep selectively benefitting negative emotional consolidation at the expense of neutral memories, with specific oscillatory events linked to this process. In contrast, the consolidation of neutral and positive memories, compared to negative memories, has been associated with increased vagally-mediated vagal heart rate variability (HRV) during wakefulness. However, how HRV during sleep contributes to emotional memory consolidation remains unexplored. We investigated how sleep oscillations and vagal contributions during sleep contribute to the consolidation of neutral and negative memories. Using a double-blind, placebo-controlled, within-subject, cross-over design, we examined the impact of pharmacological vagal suppression using zolpidem on overnight emotional memory consolidation. Thirty-two participants encoded neutral and negative pictures in the morning, followed by picture recognition tests before and after a night of sleep. Zolpidem or placebo was administered in the evening before overnight sleep, and participants were monitored with electroencephalography and electrocardiography. In the placebo condition, greater overnight improvement for neutral pictures was associated with higher vagal HRV in both Non-Rapid Eye Movement Slow Wave Sleep (NREM SWS) and REM. Additionally, the emotional memory tradeoff (i.e., difference between consolidation of neutral versus negative memories) was associated with higher vagal HRV during REM, but in this case, neutral memories were remembered better than negative memories, indicating a potential role for REM vagal HRV in promoting a positive memory bias overnight. Zolpidem, on the other hand, reduced vagal HRV during SWS, increased NREM sigma power, and eliminated the positive memory bias. Lastly, we used a stepwise linear mixed effects regression to determine how NREM sigma power and vagal HRV during REM independently explained the variance in the emotional memory tradeoff effect. We found that the addition of vagal HRV in combination with sleep significantly improved the model's fit. Overall, our results suggest that sleep brain oscillations and vagal signals synergistically interact in the overnight consolidation of emotional memories, with REM vagal HRV critically contributing to the positive memory bias.

Brain oscillations of non-rapid eye movement sleep, including slow oscillations (SO, 0.5-1.5 Hz) and spindles (10-16 Hz), mirror underlying brain maturation across development and are associated with cognition. Hence, age-associated emergence and changes in the electrophysiological properties of these rhythms can lend insight into cortical development, specifically in comparisons between pediatric populations and typically developing peers. We previously evaluated age-associated changes in SOs in male patients with Duchenne muscular dystrophy (DMD), finding a significant age-related decline between 4 and 18 years. While primarily a muscle disorder, male patients with DMD can also have sleep, cognitive, and cortical abnormalities, thought to be driven by altered dystrophin expression in the brain. In this follow-up study, we characterized the age-associated changes in sleep spindles. We found that age-dependent spindle characteristics in patients with DMD, including density, frequency, amplitude, and duration, were consistent with age-associated trends reported in the literature for typically developing controls. Combined with our prior finding of age-associated decline in SOs, our results suggest that SOs, but not spindles, are a candidate intervention target to enhance sleep in patients with DMD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Study Objectives: We sought to elucidate the interaction between sleep and mood considering menstrual cycle phase (menses and non-menses portions of the cycle) in 72 healthy young women (18-33 years) with natural, regular menstrual cycles and without menstrual-associated disorders. This work fills a gap in literature of examining mood in context of sleep and menstrual cycle jointly, rather than individually., Methods: Daily subjective measures of sleep and mood, and date of menses were remotely, digitally collected over a 2-month period. Each morning, participants rated their sleep on the previous night, and each evening participants rated the extent of positive and negative mood for that day. Objective sleep was tracked with a wearable (ŌURA ring) during month 2 of the study. Time-lag cross-correlation and mixed linear models were used to analyze the significance and directionality of the sleep-mood relationship, and how the interaction between menstrual cycle status and sleep impacted mood levels., Results: We found that menstrual status alone did not impact mood. However, subjective sleep quality and menstrual status interacted to impact positive mood (p < .05). After a night of perceived poor sleep quality, participants reported lower positive mood during menses compared to non-menses portions of the cycle, while after a night of perceived good sleep quality participants reported equivalent levels of positive mood across the cycle., Conclusions: We suggest that the perception of good sleep quality acts as a mood equalizer, with good sleep providing a protective buffer to positive mood across the menstrual cycle., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.)

Human-driven environmental changes shape ecological communities from local to global scales. Within cities, landscape-scale patterns and processes and species characteristics generally drive local-scale wildlife diversity. However, cities differ in their structure, species pools, geographies and histories, calling into question the extent to which these drivers of wildlife diversity are predictive at continental scales. In partnership with the Urban Wildlife Information Network, we used occurrence data from 725 sites located across 20 North American cities and a multi-city, multi-species occupancy modelling approach to evaluate the effects of ecoregional characteristics and mammal species traits on the urbanization-diversity relationship. Among 37 native terrestrial mammal species, regional environmental characteristics and species traits influenced within-city effects of urbanization on species occupancy and community composition. Species occupancy and diversity were most negatively related to urbanization in the warmer, less vegetated cities. Additionally, larger-bodied species were most negatively impacted by urbanization across North America. Our results suggest that shifting climate conditions could worsen the effects of urbanization on native wildlife communities, such that conservation strategies should seek to mitigate the combined effects of a warming and urbanizing world., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

This Special Feature explores the various purposes served by sleep, describing current attempts to understand how the many functions of sleep are instantiated in neural circuits and cognitive structures. Our feature reflects current experts' opinions about, and insights into, the dynamic processes of sleep. In the last few decades, technological advances have supported the updated view that sleep plays an active role in both cognition and health. However, these roles are far from understood. This collection of articles evaluates the dynamic nature of sleep, how it evolves across the lifespan, becomes a competitive arena for memory systems through the influence of the autonomic system, supports the consolidation and integration of new memories, and how lucid dreams might originate. This set of papers highlights new approaches and insights that will lay the groundwork to eventually understand the full range of functions supported by sleep.

Sleep facilitates hippocampal-dependent memories, supporting the acquisition and maintenance of internal representation of spatial relations within an environment. In humans, however, findings have been mixed regarding sleep's contribution to spatial memory and navigation, which may be due to task designs or outcome measurements. We developed the Minecraft Memory and Navigation (MMN) task for the purpose of disentangling how spatial memory accuracy and navigation change over time, and to study sleep's independent contributions to each. In the MMN task, participants learned the locations of objects through free exploration of an open field computerized environment. At test, they were teleported to random positions around the environment and required to navigate to the remembered location of each object. In study 1, we developed and validated four unique MMN environments with the goal of equating baseline learning and immediate test performance. A total of 86 participants were administered the training phases and immediate test. Participants' baseline performance was equivalent across all four environments, supporting the use of the MMN task. In study 2, 29 participants were trained, tested immediately, and again 12 h later after a period of sleep or wake. We found that the metric accuracy of object locations, i.e., spatial memory, was maintained over a night of sleep, while after wake, metric accuracy declined. In contrast, spatial navigation improved over both sleep and wake delays. Our findings support the role of sleep in retaining the precise spatial relationships within a cognitive map; however, they do not support a specific role of sleep in navigation.

Sleep is critical for health, cognition, and restorative processes, and yet, many experience chronic sleep restriction. Sleep interventions have been designed to enhance overnight sleep quality and physiology. Components of these interventions, like relaxation-based progressive muscle relaxation (PMR), have been studied in isolation and have shown direct effects on sleep architecture, including increasing time in restorative, slow-wave sleep (SWS). These relaxation methods have been understudied in naps, which are effective fatigue countermeasures that reduce deleterious effects of chronic sleep restriction. We hypothesised that PMR should boost SWS in a nap, as compared to an active control. We used a between-subject design in which healthy young adults underwent PMR training or listened to Mozart music (control) prior to a 90-min nap opportunity. We assessed changes in the amount and lateralisation of SWS, as evidence suggests left hemispheric lateralisation may be a proxy for recuperative sleep needs, and changes to state-dependent anxiety and fatigue before and after the nap to assess intervention success. We found PMR participants spent ~10 min more in SWS, equivalent to 125% more time, than the control group, and concomitantly, significantly less time in rapid eye movement sleep. PMR participants also had greater right lateralised slow-wave activity and delta activity compared to the control suggesting a more well-rested brain profile during sleep. Further, pre-sleep anxiety levels predicted nap architecture in the intervention group, suggesting benefits may be impacted by anxiety. The feasibility and accessibility of PMR prior to a nap make this an interesting research avenue to pursue with strong translational application., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Decreased functioning in the elderly is mirrored by independent changes in central and autonomic nervous systems. Additionally, recent work suggests that the coupling of these systems may also serve an important role. In young adults, Autonomic and Central Events (ACEs), measured in the temporal coincidence of heart rate bursts (HRBs) and increased slow-wave-activity (SWA, 0.5-1 Hz) and sigma activity (12-15 Hz), followed by parasympathetic surge (RR HF ) during non-rapid eye movement (NREM) sleep, predicted cognitive improvements. However, ACEs have not been examined in the elderly. Thus, the current study compared ACEs during wake and daytime sleep in older and younger adults and examined associations with working memory improvement before and after a nap. Compared to youngers, older adults showed lower amplitude of ACEs during NREM sleep, but not during wake. Furthermore, while younger adults demonstrated a parasympathetic surge after HRBs, older adults showed an earlier rise and longer maintenance of the RR HF . Taken together, our results demonstrate that autonomic-central coupling declines with age. Pathological aging implicates independent roles for decreased autonomic and central nervous system functioning, the current findings suggest that the coupling of these systems may also deserve attention., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Zolpidem, a common medication for sleep complaints, also shows secondary, unexpected memory benefits. We previously found that zolpidem prior to a nap enhanced negative, highly arousing picture memory. As zolpidem is typically administered at night, how it affects overnight emotional memory processing is relevant. We used a double-blind, placebo-controlled, within-subject, cross-over design to investigate if zolpidem boosted negative compared to neutral picture memory. Subjects learned both pictures sets in the morning. That evening, subjects were administered zolpidem or placebo and slept in the lab. Recognition was tested that evening and the following morning. We found that zolpidem maintained negative picture memory compared to forgetting in the placebo condition. Furthermore, zolpidem increased slow-wave sleep time, decreased rapid eye movement sleep time, and increased the fast spindle range in NREM. Our results suggest that zolpidem may enhance negative memory longevity and salience. These findings raise concerns for zolpidem administration to certain clinical populations., Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00079-1., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2021.)

Urban biodiversity provides critical ecosystem services and is a key component to environmentally and socially sustainable cities. However, biodiversity varies greatly within and among cities, leading to human communities with changing and unequal experiences with nature. The "luxury effect," a hypothesis that predicts a positive correlation between wealth, typically measured by per capita income, and species richness may be one indication of these inequities. While the luxury effect is well studied for some taxa, it has rarely been investigated for mammals, which provide unique ecosystem services (e.g., biological pest control) and exhibit significant potential for negative human-wildlife interactions (e.g., nuisances or conflicts). We analyzed a large dataset of mammal detections across 20 North American cities to test whether the luxury effect is consistent for medium- to large-sized terrestrial mammals across diverse urban contexts. Overall, support for the luxury effect, as indicated by per capita income, was inconsistent; we found evidence of a luxury effect in approximately half of our study cities. Species richness was, however, highly and negatively correlated with urban intensity in most cities. We thus suggest that economic factors play an important role in shaping urban mammal communities for some cities and species, but that the strongest driver of urban mammal diversity is urban intensity. To better understand the complexity of urban ecosystems, ecologists and social scientists must consider the social and political factors that drive inequitable human experiences with nature in cities., (© 2021 John Wiley & Sons Ltd.)

Objective: To develop and implement a customized toolkit within the electronic medical record (EMR) to standardize care of patients with brain tumors., Patients and Methods: We built a customized structured clinical documentation support toolkit to capture standardized data at office visits. We detail the process by which this toolkit was conceptualized and developed. Toolkit development was a physician-led process to determine a work flow and necessary elements to support best practices as defined by the neuro-oncology clinical team., Results: We have developed in our EMR system a customized work flow for clinical encounters with neuro-oncology patients. In addition to providing a road map for clinical care by our neuro-oncology team, the toolkit is designed to maximize discrete data capture. Several hundred fields of discrete data are captured through the toolkit in the context of our routine office visits. We describe the characteristics of patients seen at our clinic, the adoption of the toolkit, current initiatives supported by the toolkit, and future applications., Conclusion: The EMR can be effectively structured to standardize office visits and improve discrete data capture. This toolkit can be leveraged to support quality improvement and practice-based research initiatives at the point of care in a neuro-oncology practice., (© 2021 [Author/Employing Institution].)

Study Objectives: From childhood through adolescence, brain rhythms during non-rapid eye movement (NREM) sleep show dramatic development that mirror underlying brain maturation. For example, the function and characteristics of slow oscillations (SOs, <1 Hz) in healthy children are linked to brain development, motor skill, and cognition. However, little is known of possible changes in pediatric populations with neurologic abnormalities., Methods: We measured slow oscillations in 28 Duchenne and Becker muscular dystrophy male patients from age 4 to 20 years old during overnight in-lab clinical sleep studies. We compared our pediatric patients by age to evaluate the developmental changes of SOs from childhood to early and late adolescence., Results: Consistent with the current neuro- and physically typical literature, we found greater slow oscillation density (count of SOs per minute of each sleep stage) in NREM N3 than N2, and significantly greater slow oscillation density in frontal compared to central and occipital regions. However, separating patients into age-defined groups (child, early adolescent, and late adolescent) revealed a significant age effect, with a specific decline in the rate and amplitude of SOs., Conclusions: We found that with age, pediatric patients with Duchenne muscular dystrophy show a significant decline in slow oscillation density. Given the role that slow oscillations play in memory formation and retention, it is critical to developmentally characterize these brain rhythms in medically complex populations. Our work converges with previous pediatric sleep literature that promotes the use of sleep electroencephalographic markers as prognostic tools and identifies potential targets to promote our patients' quality of life., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

When previously consolidated hippocampally dependent memory traces are reactivated they enter a vulnerable state in which they can be altered with new information, after which they must be re-consolidated in order to restabilize the trace. The existing body of literature on episodic reconsolidation largely focuses on the when and how of successful memory reactivation. What remains poorly understood is how the nature of newly presented information affects the likelihood of a vulnerable episodic memory being altered. We used our episodic memory reconsolidation paradigm to investigate if the intention to encode impacts what subsequently becomes attributed to an older, reactivated memory. Participants learned two lists of objects separated by 48 h. We integrated a modified item-list directed-forgetting paradigm into the encoding of the second object list by cueing participants to learn some of the objects intentionally (intentional learning), while other objects were presented without a cue (incidental learning). Under conditions of memory reactivation, subjects showed equal rates of memory modification for intentionally- and incidentally-learned objects. However, in the absence of reactivation we observed high misattribution rates of incidentally-learned objects. We consider two interpretations of these data, with contrasting implications for understanding the conditions that influence memory malleability, and suggest further work that should help decide between them., (Copyright © 2020 Simon, Nadel and Gómez.)

Background: Different factors influence severity, progression, and outcomes in Parkinson's disease (PD). Lack of standardized clinical assessment limits comparison of outcomes and availability of well-characterized cohorts for collaborative studies. Methods: Structured clinical documentation support (SCDS) was developed within the DNA Predictions to Improve Neurological Health (DodoNA) project to standardize clinical assessment and identify molecular predictors of disease progression. The Longitudinal Clinical and Genetic Study of Parkinson's Disease (LONG-PD) was launched within the Genetic Epidemiology of Parkinson's disease (GEoPD) consortium using a Research Electronic Data Capture (REDCap) format mirroring the DodoNA SCDS. Demographics, education, exposures, age at onset (AAO), Unified Parkinson's Disease Rating Scale (UPDRS) parts I-VI or Movement Disorders Society (MDS)-UPDRS, Montreal Cognitive Assessment (MoCA)/Short Test of Mental Status (STMS)/Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Epworth Sleepiness Scale (ESS), dopaminergic therapy, family history, nursing home placement, death and blood samples were collected. DodoNA participants (396) with 6 years of follow-up and 346 LONG-PD participants with up to 3 years of follow-up were analyzed using group-based trajectory modeling (GBTM) focused on: AAO, education, family history, MMSE/MoCA/STMS, UPDRS II-II, UPDRS-III tremor and bradykinesia sub-scores, Hoehn and Yahr staging (H&Y) stage, disease subtype, dopaminergic therapy, and presence of autonomic symptoms. The analysis was performed with either cohort as the training/test set. Results: Patients are classified into slowly and rapidly progressing courses by AAO, MMSE score, H &Y stage, UPDRS-III tremor and bradykinesia sub-scores relatively early in the disease course. Late AAO and male sex assigned patients to the rapidly progressing group, whereas tremor to the slower progressing group. Classification is independent of which cohort serves as the training set. Frequencies of disease-causing variants in LRRK2 and GBA were 1.89 and 2.96%, respectively. Conclusions: Standardized clinical assessment provides accurate phenotypic characterization in pragmatic clinical settings. Trajectory analysis identified two different trajectories of disease progression and determinants of classification. Accurate phenotypic characterization is essential in interpreting genomic information that is generated within consortia, such as the GEoPD, formed to understand the genetic epidemiology of PD. Furthermore, the LONGPD study protocol has served as the prototype for collecting standardized phenotypic information at GEoPD sites. With genomic analysis, this will elucidate disease etiology and lead to targeted therapies that can improve disease outcomes., (Copyright © 2020 Markopoulou, Aasly, Chung, Dardiotis, Wirdefeldt, Premkumar, Schoneburg, Kartha, Wilk, Wei, Simon, Tideman, Epshteyn, Hadsell, Garduno, Pham, Frigerio and Maraganore.)

Background: We developed and implemented a structured clinical documentation support (SCDS) toolkit within the electronic medical record, to optimize patient care, facilitate documentation, and capture data at office visits in a sleep medicine/neurology clinic for patient care and research collaboration internally and with other centers., Methods: To build our SCDS toolkit, physicians met frequently to develop content, define the cohort, select outcome measures, and delineate factors known to modify disease progression. We assigned tasks to the care team and mapped data elements to the progress note. Programmer analysts built and tested the SCDS toolkit, which included several score tests. Auto scored and interpreted tests included the Generalized Anxiety Disorder 7-item, Center for Epidemiological Studies Depression Scale, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index, and the International Restless Legs Syndrome Study Group Rating Scale. The SCDS toolkits also provided clinical decision support (untreated anxiety or depression) and prompted enrollment of patients in a DNA biobank., Results: The structured clinical documentation toolkit captures hundreds of fields of discrete data at each office visit. This data can be displayed in tables or graphical form. Best practice advisories within the toolkit alert physicians when a quality improvement opportunity exists. As of May 1, 2019, we have used the toolkit to evaluate 18,105 sleep patients at initial visit. We are also collecting longitudinal data on patients who return for annual visits using the standardized toolkits. We provide a description of our development process and screenshots of our toolkits., Conclusions: The electronic medical record can be structured to standardize Sleep Medicine office visits, capture data, and support multicenter quality improvement and practice-based research initiatives for sleep patients at the point of care., Competing Interests: Competing interests The authors declare that they have no competing interests.

Objective : To use the electronic medical record (EMR) to optimize patient care, facilitate documentation, and support quality improvement and practice-based research in a concussion (mild traumatic brain injury; mTBI) clinic. Methods : We built a customized structured clinical documentation support (SCDS) toolkit for patients in a concussion specialty clinic. The toolkit collected hundreds of fields of discrete, standardized data. Autoscored and interpreted score tests include the Generalized Anxiety Disorder 7-item scale, Center for Epidemiology Studies Depression scale, Insomnia Severity Index, and Glasgow Coma Scale. Additionally, quantitative score measures are related to immediate memory, concentration, and delayed recall. All of this data collection occurred in a standard appointment length. Results : To date, we evaluated 619 patients at an initial office visit after an mTBI. We provided a description of our toolkit development process, and a summary of the data electronically captured using the toolkit. Conclusions : The electronic medical record can be used to effectively structure and standardize care in a concussion clinic. The toolkit supports the delivery of care consistent with Best Practices, provides opportunities for point of care decision support, and writes comprehensive progress notes that can be communicated to other providers.

Background and Purpose: Epilepsy patients are more likely to experience depressive symptoms and cognitive impairment compared to individuals in the general population. As the reasons for this are not definitively known, we sought to determine what factors correlate most strongly with cognition and a screening test for depression in epilepsy patients., Methods: Our study population included 379 adult patients diagnosed with epilepsy or seizure in our neurology clinic. We collected detailed demographic and clinical data during patient visits using structured clinical documentation support tools that we have built within our commercial electronic medical records system (Epic), including a depression score (Neurological Disorders Depression Inventory for Epilepsy, NDDIE) and cognition score test measures (specifically in this study, Mini-Mental State Examination [MMSE]). Medication, age, gender, body mass index, duration of epilepsy, seizure frequency, current number of anti-epileptic medications, years of education were assessed in relation to baseline score as well as change in score from initial visit to first annual follow-up., Results: Of the analyzed factors, two statistically significant associations were found after correction for multiple testing. Male gender and lower anti-seizure medication count were associated with better mood, as assessed by NDDIE score, at initial visit. Specifically, male gender was associated with a 1.3 decrease in NDDIE and for each additional anti-seizure medication, there was an associated 1.2 increase in NDDIE., Conclusions: However, these factors were not associated with change in NDDIE score from initial to first annual follow-up visit. These findings, although interesting, are preliminary. Additionally, these findings were based on a homogenous (mainly Caucasian) clinic-based population and detailed information on previous medication use was lacking. Further work is needed to replicate these findings and to understand any mechanisms that may explain these associations., Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest., (Copyright © 2019 Korean Epilepsy Society.)

Background and Purpose: Standardized electronic medical record tools provide an opportunity to efficiently provide care that conforms to Best Practices and supports quality improvement and practice-based research initiatives., Methods: We describe the development of a customized structured clinical documentation "toolkit" that standardizes patient data collection to conform to Best Practices for treating patients with stroke. The toolkit collects patients' demographic information, relevant score test measures, and captures information on disability, treatment, and outcomes., Results: We describe here our creation and implementation of the toolkits and provide example screenshots. As of August 1, 2018, we have evaluated 2332 patients at an initial visit for a possible stroke. We provide basic descriptive data gathered from the use of the toolkits, demonstrating their utility in collecting patient data in a manner that supports both quality clinical care and research initiatives., Conclusions: We have developed an EMR toolkit to support Best Practices in the care of patients with stroke. We discuss quality improvement projects and current research initiatives using the toolkit. This toolkit is being shared with other Departments of Neurology as part of the Neurology Practice-Based Research Network., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The electronic medical record (EMR) presents an opportunity to standardize patient data collection based on quality guidelines and conduct practice-based research. We describe the development of a customized EMR "toolkit" that standardizes patient data collection with hundreds of discrete fields that supports Best Practices for treating patients with memory disorders. The toolkit also supports practice-based research. We describe the design and successful implementation of a customized EMR toolkit to support Best Practices in the care of patients with memory disorders. We discuss applications, including quality improvement projects and current research initiatives, using the toolkit. This toolkit is being shared with other departments of Neurology as part of the Neurology Practice-Based Research Network. Data collection is ongoing, including longitudinal follow-up. This toolkit will generate data that will allow for descriptive and hypothesis driven research as well-quality improvement among patients seen in a memory clinic.

Long-term cuffed hemodialysis catheters are being increasingly used in the management of patients with chronic kidney disease. These tunneled catheters are available in different types and characteristics. Patients undergo imaging, primarily chest radiographs to confirm the position of the catheter tip. It is essential to be aware of the normal imaging appearances of these catheters as they may simulate pathological appearance due to the shape of their tips. This knowledge will help avoid misdiagnosis and unnecessary medical interventions.

Objectives: To demonstrate the feasibility of pragmatic clinical trials comparing the effectiveness of treatments using the electronic medical record (EMR) and an adaptive assignment design., Methods: We have designed and are implementing pragmatic trials at the point-of-care using custom-designed structured clinical documentation support and clinical decision support tools within our physician's typical EMR workflow. We are applying a subgroup based adaptive design (SUBA) that enriches treatment assignments based on baseline characteristics and prior outcomes. SUBA uses information from a randomization phase (phase 1, equal randomization, 120 patients), to adaptively assign treatments to the remaining participants (at least 300 additional patients total) based on a Bayesian hierarchical model. Enrollment in phase 1 is underway in our neurology clinical practices for 2 separate trials using this method, for migraine and mild cognitive impairment (MCI)., Results: We are successfully collecting structured data, in the context of the providers' clinical workflow, necessary to conduct our trials. We are currently enrolling patients in 2 point-of-care trials of non-inferior treatments. As of March 1, 2018, we have enrolled 36% of eligible patients into our migraine study and 63% of eligible patients into our MCI study. Enrollment is ongoing and validation of outcomes has begun., Discussion: This proof of concept article demonstrates the feasibility of conducting pragmatic trials using the EMR and an adaptive design., Conclusion: The demonstration of successful pragmatic clinical trials based on a customized EMR and adaptive design is an important next step in achieving personalized medicine and provides a framework for future studies of comparative effectiveness., Competing Interests: Conflict of interest statement. None declared.

Objective: We describe our experience with routinely capturing and analyzing Mediterranean diet data via structured clinical documentation support tools built into the electronic medical record and describe adherence to the Mediterranean diet in patients at risk for either stroke or dementia in a US neurology clinical practice., Patients and Methods: The Mediterranean diet is associated with a reduced risk of stroke and dementia. The Department of Neurology at NorthShore University HealthSystem routinely evaluates patients at initial and annual outpatient visits using structured clinical documentation support (SCDS) tools built into the electronic medical record (EMR). For patient evaluations in our Vascular Neurology and Brain Health subspecialty clinics, SCDS tools in the EMR include the validated 14-item questionnaire for Mediterranean diet adherence (PREvención con DIeta MEDiterránea [PREDIMED]) that autoscores, auto-interprets, writes to the progress note, and electronically captures data. Our study population includes patients seen at these clinics from July 1, 2015, through November 29, 2017., Results: At their initial office visit, 25.5% (95/373) of Brain Health patients scored 10 or more points ("strongly adherent") on the PREDIMED (median, 8; range, 0-14) whereas 6.7% (55/829) of Vascular Neurology patients achieved a score of 10 or more points (median, 6; range, 0-12). By contrast, 34.7% (2586/7447) of individuals in the original PREDIMED cohort were strongly adherent to the Mediterranean diet., Conclusion: PREDIMED scores can be electronically captured to tailor nutrition interventions by assessing baseline adherence at the time of their initial neurology clinic visit. Patients in our Midwestern US clinics were weakly adherent to the Mediterranean diet. This suggests a major opportunity for nutrition intervention and education in US neurology clinical practices, toward preserving and improving brain health.

Objective: Higher serum urate concentrations predict more favorable prognosis in individuals with Parkinson disease (PD). The purpose of this study was to test the causality of this association using a Mendelian randomization approach., Methods: The study was conducted among participants in DATATOP and PRECEPT, 2 randomized trials among patients with early PD. The 808 patients with available DNA were genotyped for 3 SLC2A9 single nucleotide polymorphisms (SNPs) that identify an allele associated with lower urate concentrations, and for selected SNPs in other genes encoding urate transporters that have modest or no effect on serum urate levels. An SLC2A9 score was created based on the total number of minor alleles at the 3 SLC2A9 loci. Primary outcome was disability requiring dopaminergic treatment., Results: Serum urate concentrations were 0.69mg/dl lower among individuals with ≥4 SLC2A9 minor alleles as compared to those with ≤2 (p = 0.0002). The hazard ratio (HR) for progression to disability requiring dopaminergic treatment increased with increasing SLC2A9 score (HR = 1.16, 95% confidence interval [CI] = 1.00-1.35, p = 0.056). In a comparative analysis, the HR was 1.27 (95% CI = 1.00-1.61, p = 0.0497) for a 0.5mg/dl genetically conferred decrease in serum urate, and 1.05 (95% CI = 1.01-1.10, p = 0.0133) for a 0.5mg/dl decrease in measured serum urate. No associations were found between polymorphisms in other genes associated with urate that do not affect serum urate and PD progression., Interpretation: This Mendelian randomization analysis adds to the evidence of a causal protective effect of high urate levels., (© 2014 American Neurological Association.)

Objective: Some previous studies suggest modest to strong effects of 25-hydroxyvitamin D (25(OH)D) on multiple sclerosis (MS) activity. The objective of this study was to explore the mechanistic rationale that may explain potential clinical effects of 25(OH)D., Methods: This study measured serum 25(OH)D levels and global gene expression profiles over a course of up to 2 years in patients starting treatment with interferon beta-1b (IFNB-1b) after a clinically isolated syndrome. MS disease activity was assessed by the number of gadolinium-enhancing lesions present on repeated magnetic resonance imaging (MRIs)., Results: The number of gadolinium-enhancing lesions was highly significantly associated with 25(OH)D levels. Conducting various systems-level analyses on the molecular level, multiple lines of evidence indicated that 25(OH)D regulates expression dynamics of a large gene-gene interaction system which primarily regulates immune modulatory processes modulating MS activity. The vitamin D response element was significantly enriched in this system, indicating a direct regulation of this gene interaction network through the vitamin D receptor. With increasing 25(OH)D levels, resulting regulation of this system was associated with a decrease in MS activity. Within the complex network of genes that are regulated by 25(OH)D, well-described targets of IFNB-1b and a regulator of sphingosine-1-phosphate bioavailability were found. The 25(OH)D effects on MS activity were additively enhanced by IFNB-1b., Interpretation: Here, we provide mechanistic evidence that an unbalanced 25(OH)D gene expression system may affect MS activity. Our findings support a potential benefit of monitoring and managing vitamin D levels (e.g., through supplementation) in early MS patients treated with IFN-beta-1b.

Importance: It remains unclear whether vitamin D insufficiency, which is common in individuals with multiple sclerosis (MS), has an adverse effect on MS outcomes., Objectives: To determine whether serum concentrations of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, predict disease activity and prognosis in patients with a first event suggestive of MS (clinically isolated syndrome)., Design, Setting, and Participants: The Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment study was a randomized trial originally designed to evaluate the impact of early vs delayed interferon beta-1b treatment in patients with clinically isolated syndrome. Serum 25(OH)D concentrations were measured at baseline and 6, 12, and 24 months. A total of 465 of the 468 patients randomized had at least 1 25(OH)D measurement, and 334 patients had them at both the 6- and 12-month (seasonally asynchronous) measurements. Patients were followed up for 5 years clinically and by magnetic resonance imaging., Main Outcomes and Measures: New active lesions, increased T2 lesion volume, and brain volume on magnetic resonance imaging, as well as MS relapses and disability (Expanded Disability Status Scale score)., Results: Higher 25(OH)D levels predicted reduced MS activity and a slower rate of progression. A 50-nmol/L (20-ng/mL) increment in average serum 25(OH)D levels within the first 12 months predicted a 57% lower rate of new active lesions (P < .001), 57% lower relapse rate (P = .03), 25% lower yearly increase in T2 lesion volume (P < .001), and 0.41% lower yearly loss in brain volume (P = .07) from months 12 to 60. Similar associations were found between 25(OH)D measured up to 12 months and MS activity or progression from months 24 to 60. In analyses using dichotomous 25(OH)D levels, values greater than or equal to 50 nmol/L (20 ng/mL) at up to 12 months predicted lower disability (Expanded Disability Status Scale score, -0.17; P = .004) during the subsequent 4 years., Conclusions and Relevance: Among patients with MS mainly treated with interferon beta-1b, low 25(OH)D levels early in the disease course are a strong risk factor for long-term MS activity and progression.

The primary circulating form of vitamin D is 25-hydroxy vitamin D (25(OH)D), a modifiable trait linked with a growing number of chronic diseases. In addition to environmental determinants of 25(OH)D, including dietary sources and skin ultraviolet B (UVB) exposure, twin- and family-based studies suggest that genetics contribute substantially to vitamin D variability with heritability estimates ranging from 43% to 80%. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) located in four gene regions associated with 25(OH)D. These SNPs collectively explain only a fraction of the heritability in 25(OH)D estimated by twin- and family-based studies. Using 25(OH)D concentrations and GWAS data on 5,575 subjects drawn from five cohorts, we hypothesized that genome-wide data, in the form of (1) a polygenic score comprised of hundreds or thousands of SNPs that do not individually reach GWAS significance, or (2) a linear mixed model for genome-wide complex trait analysis, would explain variance in measured circulating 25(OH)D beyond that explained by known genome-wide significant 25(OH)D-associated SNPs. GWAS identified SNPs explained 5.2% of the variation in circulating 25(OH)D in these samples and there was little evidence additional markers significantly improved predictive ability. On average, a polygenic score comprised of GWAS-identified SNPs explained a larger proportion of variation in circulating 25(OH)D than scores comprised of thousands of SNPs that were on average, nonsignificant. Employing a linear mixed model for genome-wide complex trait analysis explained little additional variability (range 0-22%). The absence of a significant polygenic effect in this relatively large sample suggests an oligogenetic architecture for 25(OH)D., (© 2012 WILEY PERIODICALS, INC.)

Previous infection with Epstein-Barr virus (EBV) and infectious mononucleosis are established multiple sclerosis (MS) risk factors, and elevated serum titers of anti-EBV nuclear antigen (anti-EBNA) antibodies in healthy adults are strongly correlated with future MS risk. In this prospective study, we investigated the association between EBV neutralizing antibodies and MS risk. MS risk tended to be higher in individuals with high titers of neutralizing antibodies compared to those with low titers (relative risk [RR] = 2.2, 95% confidence interval [CI] 0.97-5.1). This association was attenuated after adjustment for anti-EBNA1 IgG Ab titers (RR = 1.4, 95% CI 0.5-3.5). This preliminary finding warrants further study in a larger population.